Seroatlas · Human Serome Atlas

CACNA2D4

Voltage-dependent calcium channel subunit alpha-2/delta-4

Also known as: alpha2delta-4, CA2D4_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q7Z3S7
Gene: CACNA2D4
Ensembl: ENSG00000151062
Chromosome: 12
Canonical length: 1137 aa
Protein class: Disease related genes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location: Mid piece,Principal piece

OverviewNCBI Gene

This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1137 residues, UniProt reviewed canonical sequence.

>Q7Z3S7|CACNA2D4
     1  MVCGCSALLP LPNPRPTMPA TPNFLANPSS SSRWIPLQPM PVAWAFVQKT SALLWLLLLG
    61  TSLSPAWGQA KIPLETVKLW ADTFGGDLYN TVTKYSGSLL LQKKYKDVES SLKIEEVDGL
   121  ELVRKFSEDM ENMLRRKVEA VQNLVEAAEE ADLNHEFNES LVFDYYNSVL INERDEKGNF
   181  VELGAEFLLE SNAHFSNLPV NTSISSVQLP TNVYNKDPDI LNGVYMSEAL NAVFVENFQR
   241  DPTLTWQYFG SATGFFRIYP GIKWTPDENG VITFDCRNRG WYIQAATSPK DIVILVDVSG
   301  SMKGLRMTIA KHTITTILDT LGENDFINII AYNDYVHYIE PCFKGILVQA DRDNREHFKL
   361  LVEELMVKGV GVVDQALREA FQILKQFQEA KQGSLCNQAI MLISDGAVED YEPVFEKYNW
   421  PDCKVRVFTY LIGREVSFAD RMKWIACNNK GYYTQISTLA DTQENVMEYL HVLSRPMVIN
   481  HDHDIIWTEA YMDSKLLSSQ AQSLTLLTTV AMPVFSKKNE TRSHGILLGV VGSDVALREL
   541  MKLAPRYKLG VHGYAFLNTN NGYILSHPDL RPLYREGKKL KPKPNYNSVD LSEVEWEDQA
   601  ESLRTAMINR ETGTLSMDVK VPMDKGKRVL FLTNDYFFTD ISDTPFSLGV VLSRGHGEYI
   661  LLGNTSVEEG LHDLLHPDLA LAGDWIYCIT DIDPDHRKLS QLEAMIRFLT RKDPDLECDE
   721  ELVREVLFDA VVTAPMEAYW TALALNMSEE SEHVVDMAFL GTRAGLLRSS LFVGSEKVSD
   781  RKFLTPEDEA SVFTLDRFPL WYRQASEHPA GSFVFNLRWA EGPESAGEPM VVTASTAVAV
   841  TVDKRTAIAA AAGVQMKLEF LQRKFWAATR QCSTVDGPCT QSCEDSDLDC FVIDNNGFIL
   901  ISKRSRETGR FLGEVDGAVL TQLLSMGVFS QVTMYDYQAM CKPSSHHHSA AQPLVSPISA
   961  FLTATRWLLQ ELVLFLLEWS VWGSWYDRGA EAKSVFHHSH KHKKQDPLQP CDTEYPVFVY
  1021  QPAIREANGI VECGPCQKVF VVQQIPNSNL LLLVTDPTCD CSIFPPVLQE ATEVKYNASV
  1081  KCDRMRSQKL RRRPDSCHAF HPEENAQDCG GASDTSASPP LLLLPVCAWG LLPQLLR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CACNA2D4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Unknown
Secreted: No
Transmembrane segments: 1
Mean surface accessibility (rSASA): 0.28
Highest tissue expression: 19 nTPM

Expression across tissuesHPA

Tissue

retina: 19 nTPM
blood vessel: 0.4 nTPM
tongue: 0.4 nTPM
duodenum: 0.3 nTPM
placenta: 0.3 nTPM
adipose tissue: 0.2 nTPM

Single-cell type

late spermatids: 124 nCPM
early spermatids: 52 nCPM
monocytes: 12 nCPM
hofbauer cells: 11 nCPM
cone photoreceptor cells: 8.3 nCPM
macrophages: 6.4 nCPM

Immune cell

classical monocyte: 4.4 nTPM
MAIT T-cell: 4.2 nTPM
myeloid DC: 2.9 nTPM
gdT-cell: 2.1 nTPM
intermediate monocyte: 1.7 nTPM
memory CD8 T-cell: 1.5 nTPM

Brain region

thalamus: 0.6 nTPM
medulla oblongata: 0.4 nTPM
pons: 0.3 nTPM
cerebral cortex: 0.2 nTPM
choroid plexus: 0.2 nTPM
hypothalamus: 0.2 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CACNA2D4.

Disease | AllUniProt

Conditions CACNA2D4 is implicated in, by any mechanism.

Retinal cone dystrophy 4 (RCD4) MIM:610478

Disease | GeneticClinVar

7 pathogenic / likely-pathogenic of 1,351 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Retinal cone dystrophy 4
Cone dystrophy
Retinal dystrophy

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 1.01
gnomAD pLI: 0
gnomAD missense Z: 0.75
DepMap mean gene effect: 0.13
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

voltage-gated calcium channel complex

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of CACNA2D4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CACNA2D4 as an antibody target. Whether an autoantibody or antibody against CACNA2D4 could matter depends on whether native CACNA2D4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CACNA2D4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label CACNA2D4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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